This invention relates to a process for separating a compound from a mixture of different compounds.
Processes for separating compounds from mixtures are of great importance, both in the laboratory and on an industrial scale. The purity of chemical compounds is dictated to a large extent by the purification step in which a compound is separated from other products of the reaction in which it is produced. The separation of a compound from its isomers, such as its regio and geometric isomers, can be particularly difficult to achieve. Conventional methods for separating a compound from its isomers include crystallisation and chromatography but these techniques can be relatively costly and time consuming and they do not always provide a sufficiently high degree of separation.
Layered double hydroxides are a class of compounds which comprise two metal cations and have a layered structure. A brief review of layered double hydroxides is provided in Chemistry in Britain, September 1997, pages 59 to 62. The hydrotalcites, perhaps the most well-known of the layered double hydroxides, have been studied for many years.
It is known that certain organic species may be intercalated into the layers in some layered double hydroxides and into clays. For Example, Ogawa et al., in Chemistry Letters, 1992, no. 3, p. 365-368, describe the intercalation of maleic and methylmaleic acids into the clay montmorillonite in a solid state reaction. The geometrical isomers of the acids, fumaric and methylfumaric acids, were not intercalated in the solid state reaction. However, when an ethanolic solution of the two isomers was used, the montmorillonite showed no selectivity and both isomers were intercalated.
The structure of the layered materials [LiAl2(OH)6]X, where X is Cl, Br or NO3, and their hydrates has been described by Besserguenev et al., in Chem. Mater, 1997, no. 9, p. 241-247. The materials can be produced by the reaction of gibbsite [xcex3-Al(OH)3] or other forms of Al(OH)3, such as bayerite, nordstrandite or doyleite, with lithium salts of formula LiX. The materials can also be formed in other ways, such as by direct precipitation (see, for example, Serna et al, Clays and Clay Minerals, (1997), 25,384). The structure of the LiAl2(OH)6+ layers in the compounds is unusual amongst layered double hydroxides since it is based on an ordered arrangement of metal cations within the layers.
The synthesis of LiAl2(OH)6+ compounds is described in U.S. Pat. No. 4,348,295 and U.S. Pat. No. 4,348,297. The use of the materials for separating hydrocarbons and for gas chromatograph columns is taught in U.S. Pat. No. 4,430,097 and U.S. Pat. No. 4,321,065, respectively. In both of these latter two documents, the technology described does not involve intercalation chemistry but surface interactions with the stationary phase i.e., liquid-solid or gas-solid interactions.
Intercalates of compounds of formula LiOH.2Al(OH)3 are described in U.S. Pat. No. 4,727,167 and U.S. Pat. No. 4,812,245. Both documents relate to uses of the intercalates as additives to organic materials such as mineral oils.
A few other layered double hydroxides having cation ordering are known. The layered double hydroxide [Ca2Al(OH)6]2+SO42xe2x88x92 is an example.
Any improvement in the degree of selectivity or efficiency of a separation process can lead to increased purity of a product and, potentially, significant cost savings. The present invention provides a separation process which can be operated under very mild conditions and is highly selective. It also has the advantage of, in some cases, having a selectivity which is solvent and/or temperature dependent and can therefore be tuned towards a particular compound in a mixture. The process is based on the use of layered materials.
Accordingly, the present invention provides a process for separating a compound from a mixture of different compounds, the compound comprising at least two negatively charged groups connected by a linker group, which process comprises treating the mixture with a material comprising layers containing at least two different types of cation disposed in an ordered arrangement within each layer, in order to separate the compound from the mixture by selective intercalation of the compound into the material. The compound may be recovered from the intercalate formed with the material.
The layered material used in the process of the present invention contains different cations within each layer in an ordered arrangement i.e., it has cation ordering. Ordered (i.e., non-random) arrangements of cations are believed to be a major factor in the selectivity of the process. The different types of cations may be cations of different metals or cations of the same metal having different oxidation states. Preferred layered materials are compounds containing layers of formula LiAl2(OH)6+ or Ca2Al(OH)6+ with the former being particularly preferred. However, other materials containing layers having cation ordering, such as other ordered layered double hydroxides, may be expected to be useful in the process of the invention.
The compound which is separated from the mixture by intercalation into the layered material can be readily recovered by treatment of the material with an anion which intercalates between the layers in the material in preference to the compound, thereby displacing the compound. Suitable anions for this purpose include inorganic anions such as carbonate and sulphate, for example, although anions which intercalate more or less strongly than carbonate can be used. Carbonate is preferred in most cases on account of its strong capacity for binding with the material which allows the guest (i.e., intercalated) compound to be recovered substantially quantitatively and since it potentially allows the material to be regenerated by calcining the carbonate intercalate and hydrating the resulting product. Typically, treatment of the material with carbonate to recover the compound may involve treating the material with an aqueous solution of a soluble carbonate salt (e.g., sodium carbonate) at about or above room temperature for up to several hours (e.g., at 20 to 80xc2x0 C. for from 1 to 20 hours).
The intercalated compound may also be separated from the layered material in other ways. For example, the material, with the compound intercalated, may be treated in such a way as to break down the material and thereby free the compound (e.g., by treatment with a mineral acid). Alternatively, the intercalated compound may be removed by gradually protonating one or more of the negatively charged groups of the intercalated compound such that its retention within the material becomes energetically less favoured. Therefore, a further embodiment of the invention involves the recovery of the compound from the material by a method which comprises treatment with an acid under conditions which cause protonation and de-intercalation of the compound whilst leaving the layers of the material substantially intact.
The fact that the compound can be recovered from the material has clear advantages. Firstly, it allows the material to be regenerated, as mentioned above. Secondly, it means that a mixture of two compounds can be separated to provide each compound alone. For instance, a hypothetical mixture of A and B can be treated with the material to remove A from the mixture by intercalation into the material to leave behind B. The material with A intercalated is then removed from B, for example by filtration, and is treated with an anion, such as carbonate, to release A which can be readily separated from the carbonate intercalate of the material, for example by filtration. Alternatively, A could be released from its intercalate with the material by breaking down the material (e.g., by treatment with aqueous acid) and extraction of A into an organic solvent in a conventional biphasic extraction method.
The process of the invention preferably involves the treatment with the layered material of a solution of the mixture containing the compound to be separated. Suitable solvents are those which dissolve the compound. The solvents may be aqueous or non-aqueous (e.g., polar, organic solvents such as THF or acetonitrile) but, when non-aqueous solvents are used, it is preferred that they are used as mixtures with water (e.g., THF containing 10% water). The nature of the solvent can be important to the selectivity of the process. For example, when the process is used to separate a mixture of isomers, it has been found that the nature of the solvent can affect which isomer is intercalated with one isomer intercalated in some solvents and another intercalated in others.
The temperature at which the process is carried out may also affect the selectivity of the process and it has surprisingly been found that different compounds may be preferentially intercalated from the same mixture at different temperatures. Preferably, the process is carried out at temperatures from 0xc2x0 C. up to the boiling point of the solvent, more preferably 20xc2x0 C. to 100xc2x0 C. Temperatures of below 0xc2x0 C. may be employed with certain solvents having low freezing points, although the low rates of intercalation at the lower temperatures may not always provide a practically effective process.
The fact that the temperature and/or the solvent system used in the process can influence its selectivity can be used to target a particular compound for separation. Also, it means that the same material can be used to separate different compounds from the same mixture simply by varying the solvent and/or the temperature. Suitable temperatures and solvents for particular separations can be readily determined by routine experimentation in each case. Therefore, the process of the invention may involve selection of the solvent system and/or temperature so as to optimise the intercalation of the compound into the material.
The intercalation of the compound into the material can be complete in about 30 minutes to 2 hours at room temperature.
In order to effect intercalation, a solution of the mixture may be passed through the material. Conventional chromatographical and filtration techniques can be used for this purpose. For example, the layered material can be provided as a chromatographic column. The layered material may be used in the column as such or together with a support (e.g., the material embedded in resin beads). Addition of a mixture to the column leads to the elution of non-intercalated compound or compounds from the column with the intercalated compound retained. Eluting with an anion which intercalates in preference to the already intercalated compound de-intercalates the adsorbed compound. The column may then be reactivated (e.g., by calcination or, in the case of [LiAl2(OH)6]+ layered materials, addition of concentrated LiCl solution or HCl solution). Alternatively, the mixture may be treated with the material in other ways such as, for example, by stirring a suspension of the material in the mixture.
The process of the invention can be used to separate a compound from one or more other structurally related or unrelated compounds having the same or different functional groups. The process of the invention has been found to be particularly suitable for the separation of a compound from a mixture of the compound and its isomers and this is, therefore, a preferred feature of the process. Preferably, the isomers are geometric isomers or regio-isomers. Mixtures of this type can be difficult to separate effectively using conventional methods. Alternatively, the isomers may be diastereoisomers or optical isomers; using materials having chiral structures, for example formed in the presence of a chiral guest template, it is possible to separate the different optical isomers of a compound. Layered materials suitable for separating optical isomers can be, for example, second stage intercalates (i.e., materials having intercalation in every other layer) which have chiral molecules (such as the anions of optically active diacids e.g., malic or tartaric acid) in every other layer; the optical isomers to be separated intercalate into the layers not already occupied by the chiral molecules.
The process of the invention may also be used in other separation processes, such as the separation of dianions from a mixture containing monoanions, for example. The dianions may be present as the minor or major component of the mixture.
The compounds intercalated into the material in the process of the invention comprise at least two negatively charged groups connected by a linker group. Since the compounds have at least two negatively charged groups (they may contain more than two negatively charged groups, but they preferably contain two), they are anionic although the anions may be formed solely for the purpose of the separation process. The negatively charged groups may be the anionic groups formed by the deprotonation of an acid, such as carboxylate (CO2xe2x88x92) and oxoanions of phosphorous and sulphur (e.g., phosphonate (xe2x80x94PO32xe2x88x92), phosphate (xe2x80x94OPO32xe2x88x92), sulphate (xe2x80x94OSO3xe2x88x92) and sulphonate (xe2x80x94SO3xe2x88x92)) or by the deprotonation of less acidic groups (e.g., alkoxide or phenolate) but are preferably carboxylate or sulphonate groups, more preferably carboxylate groups. The negatively charged groups in the compound may be the same or different. The linker group in the compounds provides connection between the negatively charged groups. The linker group may be wholly flexible (e.g., an alkylene chain) or it may have a degree of rigidity (e.g., an alkenylene chain). Preferably, the linker group provides a substantially rigid connection between the negatively charged groups to keep them at a substantially fixed distance apart. Suitable linker groups which provide a rigid connection include, for example, phenylene, naphthalene and other carbocyclic or heterocyclic, polyaromatic or non-aromatic, ring structures and 1,2-ethylene, each optionally substituted.
The process of the invention may be used to separate a wide variety of different types of compound including surfactants and biological molecules such as amino acids, sugars and polynucleotides, for example.
The process of the invention has been found to be particularly effective for the separation of the dianion of 1,4-benzenedicarboxylic acid from mixtures, for example mixtures comprising its 1,2- and 1,3-isomers and for the separation of the dianion of fumaric acid (i.e., trans-but-2-enedioic acid) from mixtures, for example mixtures comprising its cis-isomer, the dianion of maleic acid. The selectivity of materials containing layers having ordered cations in these separation processes is greater than 95% as determined by 1H nmr. The separation of the 1,4-benzenedicarboxylic dianion from its isomers and the separation of maleate dianions from fumarate dianions are therefore preferred features of the process. The process of the invention thus enables the separation of the isomers of benzenedicarboxylic acids to be achieved, simply by forming the dianions from the acids by treatment with an alkali at a suitable pH for deprotonation of both of the acid groups. Similarly, fumaric and maleic acids may be separated by the process of the invention following the formation of their dianions in the same way. After the separation has been achieved, the acids may be reformed by protonation, for example using a mineral acid. Suitable water soluble benzenedicarboxylate, fumarate and maleate anions, which allow the process to be carried out in aqueous solution, are provided by the disodium salts.
The process is equally effective for other separations such as the separation of 1,5- and 2,6-naphthalenedisulphonates and 1,2- and 1,3-benzenedisulphonates, for example.
The material which is used in the process of the invention may be any substance which contains layers having at least two different cations within each layer with the cations ordered within the layers. The materials must, of course, be capable of intercalating the compound to be separated. Examples of suitable materials are compounds of formula [LiAl2(OH)6]A, having ordered [LiAl2(OH)6]+ layers, wherein A is OH, F, Cl, Br, I, (SO4)xc2xd or NO3, optionally hydrated with stoichiometric or non-stoichiometric amounts of water, such as [LiAl2(OH)6]Cl.H2O. The anion A is generally intercalated between the layers and must be capable of being displaced by the binding of the compound between the layers.
Without wishing to be bound by theory, it is believed that the selectivity of the layered materials may stem from the differing packing energies of the guest compounds within the interlayer region and their interactions with the positively charged, ordered layers. When benzenedicarboxylate dianions or mixtures of maleate and fumarate dianions are treated with [LiAl2(OH)6]A, for example, experimental results show that all of the anions are initially intercalated into the layers but that the layers subsequently contract to expel substantially all of the dianions except the favoured 1,4-benzenedicarboxylate and fumarate dianions.
FIGS. 1, 2 and 3 show, schematically, what is believed to be the mechanism underlying the separation process of the invention.